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Abstract:

The present disclosure relates to novel compositions which provide
improved nutritional support for premenopausal and menopausal women
and/or relief from systems associated with menopause, as well as
prophylactic effects, and methods for using same.

Claims:

1. A composition for supplementing the diet, the composition comprising:a.
docosahexaenoic acid in an amount of from about 10 mg to about 1000 mg;
andb. a calcium compound present in an amount such that the ratio of
docosahexaenoic acid to calcium compound is from about 1:0.4 to 1:250.

2. A composition for administration to premenopausal and menopausal women,
the composition comprising:a. docosahexaenoic acid in an amount of from
about 10 mg to about 1000 mg; andb. a calcium compound present in an
amount such that the ratio of docosahexaenoic acid to calcium compound is
from about 1:0.4 to 1:250.

3. A method for providing nutritional supplementation to a menopausal
woman, which comprises:a. docosahexaenoic acid in an amount of from about
10 mg to about 1000 mg; andb. a calcium compound present in an amount
such that the ratio of docosahexaenoic acid to calcium compound is from
about 1:0.4 to 1:250.

4. A method for providing nutritional supplementation to a premenopausal
woman, which comprises:a. docosahexaenoic acid in an amount of from about
10 mg to about 1000 mg; andb. a calcium compound present in an amount
such that the ratio of docosahexaenoic acid to calcium compound is from
about 1:0.4 to 1:250.

Description:

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001]This application is a continuation application of co-pending U.S.
patent application Ser. No. 11/023,871 filed Dec. 22, 2004, said
application being a continuation of U.S. patent application Ser. No.
10/131,236, filed Apr. 25, 2002; said application being a continuation of
U.S. patent application Ser. No. 09/409,059, filed Sep. 30, 1999 now
issued as U.S. Pat. No. 6,479,545, the entire contents of which are
hereby incorporated by reference in their entirety.

BACKGROUND OF THE INVENTION

[0002]The present invention is directed to novel compositions for use by
premenopausal women and menopausal women for the purpose of providing
improved nutritional support and/or relief from the symptoms of
menopause, as well as to methods for using same.

[0003]Menopause, the transition from the reproductive stage to the
non-reproductive stage of a woman's life, is characterized primarily by
the cessation of menstruation. However, menopause has come to signify
much more than simply the loss of reproductive capability, as it is also
associated with a number of acute and chronic conditions.

[0004]Menopausal syndrome consists of a number of varying and often highly
distressing symptoms resulting from hormonal imbalance and nutritional
deficiency in the female body.

[0005]Hot flashes and sweating secondary to vasomotor instability affect
75% of women. Psychologic and emotional symptoms of fatigue, insomnia,
irritability and nervousness are common. Lack of sleep due to disturbance
by recurring hot flashes contributes to fatigue and irritability.
Dizziness, parenthesis and cardiac symptoms of palpitations and
tachycardia may also occur; the incidence of heart disease increases.
Other common symptoms include nausea, constipation, diarrhea, arthralgia
.and myalgia. The Merck Manual, 1793 (16th Ed. 1992).

[0006]Menopause is also characterized by osteoporosis, or loss of bone
density, resulting in increased bone fractures and vertebral column
collapse. Bone loss begins around age 35. This loss accelerates during
menopause, which generally occurs around age 45 to 55. Bone mass losses
average 1-2% each year after menopause. Primary sites are the vertebrae,
which show anterior collapse resulting in stooping and backache, the hips
and the wrist. The Merck Manual 1793(16th Ed. 1992). Osteoporosis
develops over decades and is related to peak bone mass, as well as to the
degree of bone loss.

[0007]Estrogen replacement therapy has been used to relieve the symptoms
of menopause. The Merck Manual 1793(16th Ed. 1992). However,
estrogen therapy is not without its limitations. In some instances the
side effects of estrogen therapy can be quite severe. These side effects
include increased risk of certain cancers, such as breast cancer.
Estrogen has also been implicated in certain endometrial cancers.
Although treatments with progestin have been shown to counter these
adverse side effects, postmenopausal women treated with such an
estrogen-progestin regimen frequently experience undesirable uterine
bleeding. Further, hormone therapy alone is insufficient to meet the
varied and heightened nutritional requirements of a woman during this
phase in her life. Adequate nutritional intake is also necessary.

[0008]Appropriate nutritional intake is increasingly important to
menopausal women. For example, adequate calcium intake prevents
osteoporosis. Moreover, certain vitamins and minerals enhance calcium
absorption and utilization. However, while vitamin and mineral
supplements providing calcium for women is known in the art, conventional
supplements fail to meet other nutritional requirements of menopausal
women. Specifically, conventional supplements lack certain fatty acids
which are especially useful to treat symptoms of fatigue or tiredness
commonly experienced by a woman undergoing menopause. Fatty acids are
essential in supporting life's activities as the body derives most of its
energy from triglycerides, a molecule of glycerol with three fatty acids.
Linoleic acid and linolenic acid, in particular, are two fatty acids
which are indispensable to body functions. The inclusion of these two
fatty acids in nutritional supplements is of particular significance
because they are not produced by the body and must be supplied through
food. However, conventional nutritional supplements fail to include these
two fatty acids.

[0009]The use of fatty acids in various forms and for various purposes has
been previously disclosed. Horrobin et al. disclose a method of
prevention or treatment of endometriosis wherein effective amounts of one
or both gamma-linolenic acid and/or dihomo-gamma-linolenic acid are
administered to women. Specifically, the fatty acids may be administered
in the form of the acid itself or as an ester, amide, salt or any other
functional derivative capable of being converted to the acid within the
body and may be from natural or synthetic sources.

[0010]Maxson et al., U.S. Pat. No. 4,900,734, disclose a pharmaceutical
composition containing estradiol and progesterone for oral
administration. Specifically, the pharmaceutical composition comprises
estradiol dissolved in an oil vehicle containing a suspension of
micronized progesterone. Further, the oil vehicle is high in glycerides
of polyunsaturated fatty acids. Specifically, linoleic and linolenic
acids are disclosed as particularly effective polyunsaturated fatty
acids. The combined administration of these steroids is disclosed as
being useful for replacement hormone therapy in the treatment of
menopausal women.

[0011]Cohen, U.S. Pat. No. 4,945,103, discloses a method for treating
women who suffer from premenstrual syndrome (PMS) which comprise
administration of melatonin in sufficient doses to relieve symptoms
associated with PMS. Specifically, Cohen discloses that progestogen can
be administered in combination with melatonin. Further, melatonin can
administered to women orally, parenterally or in the form of an implant.
Cohen specifically discloses that PMS may be linked to a nutritional
deficiency in either vitamin B-complex, especially vitamin B6
(pyroxidine), or essential fatty acids, especially linolenic acid.

[0012]Horrobin, U.S. Pat. No. 5,380,757, discloses a method of treatment
of vulvar dystrophy and/or vaginal dryness, which medicament comprises
gamma-linolenic (GIA) and/or dihomo-gamma-linolenic acid (DGIA),
optionally in association with other essential fatty acids of the n-6 or
n-3 series. Horrobin discloses that deficiency of linoleic acid in the
diet may produce atrophy and hyperkeratosis of the skin.

[0013]Miyamoto et al., U.S. Pat. No. 5,461,170, disclose a glyceride
preparation having a branched saturated fatty acid and/or myristic acid
residues for use in liquid oils and/or solid cosmetics of the same.
Specifically, Miyamoto et al. disclose a polyol fatty-acid ester having
mixed acid group produced by reacting a partial ester of a polyol and a
branched fatty acid with a straight chain fatty acid or a lower alcohol
ester thereof in the presence of a lipase. The obtained glyceride mixture
contains a large amount of diglyceride having a branched, saturated fatty
acid group, and a straight chain, fatty acid group. The reference does
not specifically disclose either linoleic or linolenic acid and/or
menopause.

[0015]Shylankevich, U.S. Pat. No. 5,569,459, discloses compositions
containing various vitamins, minerals and herbal extracts that can be
used for alleviation of premenstrual syndrome, menopausal disorders, and
stimulating estrogen production. Specifically, the invention relates to
such pharmaceutical compositions and dietary supplements that contain
natural soybean phytoestrogens of the isoflavone group.

[0017]However, the previously disclosed formulations are deficient for
various reasons. In particular, none of the previously disclosed
formulations contain critical components, such as essential fatty acids
or calcium, in amounts specifically tailored to meet the needs of
premenopausal and menopausal women. Moreover, the previously disclosed
formulations fail to disclose the significance of the proportion of the
various components to one another. Therefore, there is a need for
formulations specifically tailored to meet the needs of menopausal women.
Further, there is a need for drug delivery regimens which are
specifically adapted to meet the needs of premenopausal and menopausal
women.

SUMMARY OF THE INVENTION

[0018]The compositions of the present inventive subject matter overcome
the deficiencies of currently-available nutritional supplements by
providing formulations and drug delivery regimens which are specifically
tailored for women just prior to, during and after the period of
menopause. The present compositions contain a novel combination of
various components, such as fatty acids, in critical ratios and amounts,
optionally in combination with various vitamins and minerals.

[0019]One embodiment of the present inventive, subject matter is a
composition for administration to a menopausal woman, which comprises:

[0020]an essential fatty acid compound selected from the group consisting
of a linoleic acid compound, a linolenic acid compound, a docosahexaenoic
acid compound, an omega-3 fatty acid compound, an omega-2 fatty acid
compound, a derivative thereof and a combination thereof in an amount of
about 10 mg to about 1,000 mg;

[0021]a calcium compound or derivative thereof in an amount of about 400
mg to about 2500 mg;

[0022]a folic acid compound or derivative thereof in an amount of about
0.4 mg to about 5.0 mg; and,

[0023]wherein the weight ratio of the essential fatty acid compound to the
calcium compound or derivative thereof is about 1:0.4 to 250 in a single
or multiple dosage unit.

[0024]Another embodiment of the present inventive subject matter is a
composition for administration to a menopausal woman, which comprises:

[0025]a first fatty acid compound selected from the group consisting of a
linoleic acid compound, a derivative thereof and a combination thereof in
an amount of about 10 mg to about 1,000 mg;

[0026]a second fatty acid compound selected from the group consisting of a
linolenic acid compound, a derivative thereof and combinations thereof in
an amount of about 10 mg to about 1,000 mg;

[0027]a third fatty acid compound selected from the group consisting of a
docosahexaenoic acid compound, an omega-3 fatty acid, an omega-2 fatty
acid, a derivative thereof and a combination thereof in an amount of
about 10 mg to about 1,000 mg;

[0028]a calcium compound or derivative thereof in an amount of about 400
mg to about 2500 mg;

[0029]a folic acid compound or derivative thereof in an amount of about
0.4 mg to about 5.0 mg;

[0030]wherein the weight ratio of the sum of the amounts of said first and
second fatty acid compounds to the amount of said third fatty acid
compound is about 1:0.5 to 1.5; and

[0031]wherein the weight ratio of the sum of the amounts of said first,
second and third fatty acid compounds to the amount of said calcium
compound or derivative thereof is about 1:0.4 to 50.

[0032]A further embodiment of the present inventive subject matter is a
composition for administration to a menopausal woman, which comprises:

[0033]a first fatty acid compound selected from the group consisting of a
linoleic acid compound, a derivative thereof and a combination thereof in
an amount of about 10 mg to about 1,000 mg;

[0034]a second fatty acid compound selected from the group consisting of a
linolenic acid compound, a derivative thereof and combinations thereof in
an amount of about 10 mg to about 1,000 mg;

[0035]a third fatty acid compound selected from the group consisting of a
docosahexaenoic acid compound, an omega-3 fatty acid, and omega-2 fatty
acid, a derivative thereof and a combination thereof in an amount of
about 10 mg to about 1,000 mg;

[0036]a calcium compound or derivative thereof in an amount of about 400
mg to about 2500 mg;

[0037]a vitamin C compound or derivative thereof in an amount of about 25
mg to about 500 mg;

[0038]a vitamin E compound or derivative thereof in an amount of about 10
mg to about 500 mg;

[0039]wherein the weight ratio of the sum of the amounts of said first and
second fatty acid compounds to the amount of said third fatty acid
compound is about 1:0.5 to 1.5; and

[0040]wherein the weight ratio of the sum of the amounts of said first,
second and third fatty acid compounds to the amount of said calcium
compound or derivative thereof is about 1:0.4 to 50.

[0041]An even further embodiment of the present inventive subject matter
is a composition for administration to a menopausal woman, which
comprises:

[0042]a first fatty acid compound selected from the group consisting of a
linoleic acid compound, a derivative thereof and a combination thereof in
an amount of about 10 mg to about 1,000 mg;

[0043]a second fatty acid compound selected from the group consisting of a
linolenic acid compound, a derivative thereof and combinations thereof in
an amount of about 10 mg to about 1,000 mg;

[0044]a third fatty acid compound selected from the group consisting of a
docosahexaenoic acid compound, an omega-3 fatty acid, an omega-2 fatty
acid, a derivative thereof and a combination thereof in an amount of
about 10 mg to about 1,000 mg;

[0045]a calcium compound or derivative thereof in an amount of about 400
mg to about 2500 mg;

[0046]a folic acid compound or derivative thereof in an amount of about
0.4 mg to about 5.0 mg;

[0047]a vitamin C compound or derivative thereof in an amount of about 25
mg to about 500 mg;

[0048]a vitamin E compound or derivative thereof in an amount of about 10
mg to about 500 mg;

[0049]a vitamin A compound or derivative thereof in an amount of about
2,500 IU to about 6,500 IU;

[0050]wherein the weight ratio of the sum of the amounts of said first and
second fatty acid compounds to the amount of said third fatty acid
compound is about 1:0.5 to 1.5; and;

[0051]wherein the weight ratio of the sum of said first, second and third
fatty acid compounds to the amount of said calcium compound or derivative
thereof is about 1:0.4 to 50.

[0052]Another embodiment of the present inventive subject matter is a
composition for administration to a menopausal woman, which comprises:

[0053]a first fatty acid compound selected from the group consisting of a
linoleic acid compound, a derivative thereof and a combination thereof in
an amount of about 10 mg to about 1,000 mg;

[0054]a second fatty acid compound selected from the group consisting of a
linolenic acid compound, a derivative thereof and combinations thereof in
an amount of about 10 mg to about 1,000 mg;

[0055]a third fatty acid compound selected from the group consisting of a
docosahexaenoic acid compound, an omega-3 fatty acid, an omega-2 fatty
acid, a derivative thereof and a combination thereof in an amount of
about 10 mg to about 1,000 mg;

[0056]a calcium compound or derivative thereof in an amount of about 400
mg to about 2500 mg;

[0057]a folic acid compound or derivative thereof in an amount of about
0.4 mg to about 5.0 mg;

[0058]a vitamin C compound or ester derivative thereof in an amount of
about 25 mg to about 500 mg;

[0059]a vitamin E compound or derivative thereof in an amount of about 10
mg to about 500 mg;

[0060]a vitamin B6 compound or derivative thereof in an amount of about 10
mg to about 50 mg;

[0061]a vitamin B12 compound or derivative thereof in an amount of about
25 mcg to about 75 mcg;

[0062]a vitamin D compound or derivative thereof in an amount of about 200
IU to about 625 IU;

[0063]wherein the weight ratio of the sum of the amounts of said first
.and second fatty acid compounds to the amount of said third fatty acid
compound is about 1:0.5 to 1.5; and

[0064]wherein the weight ratio of the sum of the amounts of said first,
second and third fatty acid compounds to the amount of said calcium
compound or derivative thereof is about 1:0.4 to 50.

[0065]Yet another embodiment of the present inventive subject matter is a
composition for administration to a menopausal woman, which comprises:

[0067]a calcium compound or derivative thereof in an amount of about 400
mg to about 2500 mg;

[0068]a folic acid compound or derivative thereof in an amount of about
0.4 mg to about 5.0 mg.

[0069]A further embodiment of the present inventive subject matter is a
drug delivery regimen, which comprises:

[0070]a first dosage form comprising a first biologically active substance
to be administered to a menopausal woman at a predetermined time period;

[0071]a second dosage form comprising a second biologically active
substance to be administered to the menopausal woman simultaneously with
said first dosage form;

[0072]wherein said first biologically active substance and said second
biologically active substance are incompatible substances.

[0073]An additional embodiment of the present inventive subject matter is
a method for providing nutritional supplementation to a menopausal woman,
which comprises: administering an essential fatty acid compound to the
woman during the period commencing at the onset of menopause, said
essential fatty acid compound being selected from the group consisting of
a linoleic acid compound, a linolenic acid compound, a docosahexaenoic
acid compound, an omega-3 fatty acid compound, an omega-2 fatty acid
compound, a derivative thereof and a combination thereof;

[0074]administering about 400 mg co about 2500 mg of a calcium compound or
derivative thereof to the woman during the period commencing at the onset
of menopause;

[0075]administering about 0.4 mg to about 5.0 mg of a folic acid compound
or derivative thereof to the woman during the period commencing at the
onset of menopause; and

[0076]wherein the weight ratio of the essential fatty acid compound to the
calcium compound or derivative thereof is about 1:0.4 to 250.

[0077]Another embodiment of the present inventive subject matter is a
method for providing nutritional supplementation to a menopausal woman,
which comprises:

[0078]administering a first fatty acid compound to the woman during a
period commencing at the onset of menopause, said first fatty acid
compound being selected from the group consisting of a linoleic acid
compound, a derivative thereof and a combination thereof;

[0079]administering a second fatty acid compound to said woman during the
period commencing at the onset of menopause, said second fatty acid
compound being selected from the group consisting of a linolenic acid
compound, a derivative thereof and a combination thereof;

[0080]administering a third fatty acid compound to said woman during the
period commencing at the onset of menopause, said third, fatty acid
compound being selected from the group consisting of a docosahexaenoic
acid compound, an omega-3 fatty acid, an omega-2 fatty acid, a derivative
thereof and a combination thereof, and said third fatty acid compound
being provided to the woman together with said first and second fatty
acid compounds;

[0081]administering about 400 mg to about 2500 mg of a calcium compound or
derivative thereof to said woman;

[0082]wherein the weight ratio of the sum of the amounts of said first and
second fatty acid compounds to the amount of said third fatty acid
compound is about 1:0.5 to 1.5; and

[0083]wherein the weight ratio of the sum of the amounts of said first,
second and third fatty acid compound to the amount of said calcium
compound or derivative thereof is about 1:0.4 to 50.

[0084]Yet another embodiment of the present inventive subject matter is a
method for providing nutritional supplementation to a menopausal woman
while reducing symptoms associated with menopause, which comprises:

[0085]administering a first fatty acid compound to the woman during a
period commencing at the onset of menopause, said first fatty acid
compound being selected from the group consisting of a linoleic acid
compound, a derivative thereof and a combination thereof;

[0086]administering a second fatty acid compound to said woman during the
period commencing at the onset of menopause, said second fatty acid
compound being selected from the group consisting of a linolenic acid
compound, a derivative thereof and a combination thereof;

[0087]administering a third fatty acid compound to said woman during the
period commencing at the onset of menopause, said third fatty acid
compound being selected from the group consisting of a docosahexaenoic
acid compound, an omega-3 fatty acid, an omega-2 fatty acid, a derivative
thereof and a combination thereof, and said third fatty acid compound
being provided to the woman together with said first and second fatty
acid compounds;

[0088]administering about 400 mg to 2500 mg of a calcium compound or
derivative thereof to said woman;

[0089]administering a therapeutic substance to said woman;

[0090]wherein the weight ratio of the sum of the amounts of said first and
second fatty acid compounds to the amount of said third fatty acid
compound is about 1:0.5 to 1.5; and

[0091]wherein the weight ratio of the sum of said first, second and third
fatty acid compound to the amount of said calcium compound or derivative
thereof is about 1:0.4 to 50.

[0092]A further embodiment is a method for delaying the onset of
menopause, which comprises: administering an essential fatty acid to a
woman prior to menopause, said fatty acid being selected from the group
consisting of a linoleic acid compound, a linolenic acid compound, a
docosahexaenoic acid compound, an omega-3 fatty acid compound, an omega-2
fatty acid compound, a derivative thereof and a combination thereof;
wherein said essential fatty acid is administered in an amount sufficient
to delay the onset of menopause.

[0093]A still further embodiment is a method for providing, nutritional
supplementation to a menopausal woman while reducing symptoms associated
with menopause, which comprises:

[0094]administering a fatty acid compound to the woman during a period
commencing at the onset of menopause, said fatty acid compound being
selected from the group consisting of a linoleic acid compound, a
linolenic acid compound, a docosahexaenoic acid compound, an omega-3
fatty acid, an omega-2 fatty acid, a derivative thereof and a combination
thereof;

[0095]administering about 400 mg to 2500 mg of a calcium compound or
derivative thereof to said woman;

[0096]and administering a non-nutritional active to said woman.

[0097]Another embodiment is a method for reducing the possibility of
premature menopause, which comprises: administering an essential fatty
acid to a woman prior to menopause, said fatty acid being selected from
the group consisting of a linoleic acid compound, a linolenic acid
compound, a docosahexaenoic acid compound, an omega-3 fatty acid
compound, an omega-2 fatty acid compound, a derivative thereof and a
combination thereof; wherein said essential fatty acid is administered in
an amount sufficient to reduce the risk of premature menopause.

[0098]An additional embodiment is a method for providing nutritional
supplementation to a premenopausal woman or a menopausal woman, which
comprises: administering to the premenopausal woman or menopausal woman a
biologically active substance for treating symptoms of menopause;
administering to the premenopausal woman or menopausal woman a calcium
compound or derivative thereof in an amount of 400 mg to about 2500; and
administering to the premenopausal woman or menopausal woman a folic acid
compound or derivative thereof in an amount of about 0.4 mg to about 5.0
mg.

DETAILED DESCRIPTION OF THE INVENTION

[0099]As used herein, "menopausal woman" refers to any woman who has
experienced ovarian failure. The ovarian failure can be measured by blood
tests for low estrogen levels (estradiol) or elevated gonadotropin levels
(follicle stimulating hormone). When menopause occurs it remains for the
life of the woman. The term "menopause" also encompasses the
postmenopause or the postmenopausal period. The term "menopause" also
encompasses natural menopause and artificial menopause.

[0100]"Premenopausal woman" refers to any woman during the period
commencing five years prior to onset of menopause.

[0101]"Nutritional status" refers to the levels of vitamins, minerals and
other nutrients which will be available for use by the menopausal woman.

[0102]"Nutritional status" refers to the presence or absence of any
nutrient deficiency, or in other words, the extent to which physiological
nutrient demands are being satisfied such that deficiency is avoided.

[0103]"Optimize neurological development" refers to attainment of the
highest degree of neurological development possible through natural
processes without the use of any unnatural substances or procedures, such
as drugs, surgery and the like.

[0104]"Biologically active substance" refers to any substance or
substances comprising a drug, active therapeutic substance, metabolite,
medicament, vitamin, or mineral, any substance used for treatment,
prevention, diagnosis, cure or mitigation of disease or illness, any
substance which affects anatomical structure or physiological function,
or any substance which alters the impact of external influences on an
animal, or metabolite thereof, and as used herein, encompasses the terms
"active substance", "therapeutic substance", "agent", "active agent",
"drug", "medication", "medicine", "medicant", and other such similar
terms.

[0105]"Non-nutritional active" refers to any substance or substances
comprising a drug, active therapeutic substance, metabolite, or
medicament, or any other substance used for treatment, prevention,
diagnosis, cure or mitigation of disease or illness, any substance which
affects anatomical structure or physiological function, or any substance
which alters the impact of external influences on an animal, or
metabolite thereof, and as used herein, that is not a vitamin, mineral,
or any other nutritional compound or compositions.

[0106]"Specific physiological needs" refers to the unique requirements for
certain levels of certain nutrients by one class of persons, such as
menopausal women, premenopausal women, postmenopausal women, etc., as
distinguished from other classes.

[0107]"Biologically-acceptable" refers to being safe for human
consumption.

[0108]"Storage-incompatible substances" refers to substances that may not
be formulated together in a single dosage unit or stored together in
direct contact because the substances will interact in a negative manner
and also substances that cannot be formulated together in a single dosage
unit because the sum total of the dosage amounts of the substances would
result in a single dosage unit which is too large to be swallowed. The
term also refers to substances which may be stored in direct contact,
however, one of the substances is preferably formulated in a dosage form
which is either not preferred or incompatible with the other substance.
Storage-incompatibility also refers to two or more substances wherein at
least one substance is a prescription substance and at least one
substance is a non-prescription substance.

[0109]"Storage-incompatibility refers to the state that exists between
storage-incompatible substances, as defined above.

[0110]The compositions of the present inventive subject matter provide
several specific new and unexpected benefits. First, the formulations
ensure that menopausal women are provided with adequate energy during the
period of menopause. Secondly, the formulations allow the menopausal
women to maintain the adequate fatty acid stores for both her future use.
Thirdly, the fatty acids optimize the neurological maintenance of the
menopausal women. Fourthly, when administered just prior to menopause,
the present compositions prepare women for the increased physiological
demands and stresses to be placed upon their bodies. Additionally, the
present compositions provide nutritional supplementation to women during
the early stage of menopause known as premenopause.

[0111]Finally, the present compositions help minimize the risk of
menopause related disorders and symptoms resulting from such disorders.

[0112]The present inventive subject matter is based, in part, on the
discovery that when compositions having certain fatty acids, in certain
amounts and proportions to one another, are administered to women just
prior to, during and after menopause, the women will achieve optimal
nutritional supplementation. In particular, supplementing a menopausal
woman's diet with the formulations described below for a period
commencing when symptoms of menopause are actually experienced, or
preferably just prior to when menopause would generally be expected, will
ensure that the woman has adequate essential fatty acids for present and
future use. The fatty acid supplement may also further contain vitamins
and minerals to confer added health benefits to the menopausal woman. In
addition to benefiting humans, the present invention can also benefit
non-human mammals. The composition of the present invention could be
administered to a mammal in animal feed, pill form, or other appropriate
dosage forms to such mammals.

[0113]Without being limited by theory, the present compositions stimulate
or play a vital role in one or more natural biological pathways. For
example, the arachidonic acid cascade may play a significant role in the
support and maintenance of a menopausal woman's health. Specifically, in
the arachidonic acid cascade, linoleic acid is converted first to
gamma-linolenic acid and then to further metabolites such as
dihomo-gamma-linolenic acid and arachidonic acid which are precursors of
1 and 2 series prostaglandin respectively, as shown in the outline below:

##STR00001##

[0114]The present composition may contain an essential fatty acid
compound. The fatty acid compound may be a linoleic acid compound,
derivatives thereof or any combination of linoleic acid and/or linoleic
acid derivatives. The fatty acid compound may be a linolenic acid
compound, derivatives thereof and/or an combinations of linolenic acid
and/or linoleic acid derivatives. The fatty acid compound may also be a
docosahexaenoic acid compound, an omega-3 fatty acid compound, an omega-2
fatty acid compound, derivatives thereof or combinations thereof. The
fatty acid may further be a combination of any of the above discussed
fatty acids.

[0115]Preferably, the fatty acid compound is present in the composition in
an amount ranging from about 10 mg to 1,000 mg. More preferably, the
fatty acid compound is present in the composition in an amount ranging
from about 15 mg to 200 mg, independently of the other fatty acid
compounds. Even more preferably, the fatty acid compounds is present in
the composition in an amount ranging from about 20 mg to about 100 mg,
independently of the other fatty acid compounds. Most preferably, the
fatty acid compound is present in the composition in an amount ranging
from about 25 mg to 50 mg, independently of the other fatty acid
compounds.

[0116]Three fatty acid compounds may be present in the present composition
in critical proportions to one another. Preferably, the weight ratio of
the sum of the amounts of said first and second fatty acid compounds to
the amount of said third fatty acid compound is about 1:0.5 to 1.5. More
preferably, the weight ratio of the sum of the amounts of said first and
second fatty acid compound is about 1:0.7 to 1.3. Even more preferably,
the weight ratio of the sum of the amounts of said to the amount of said
third fatty acid compound is about 1:0.9 to 1.2. Most preferably, the
weight ratio of the sum of the amounts of said first and second fatty
acid compounds to the amount of said third fatty acid compound is about
1:0.9 to 1.1.

[0117]The compositions of the present invention may incorporate any
compound that can react with an essential fatty acid to form a
biochemically active compound. Preferably, the compound is a compound
which fulfills a nutritional need, for example, without limitation,
sphingomyelin, myelin, derivatives thereof and combinations thereof.

[0120]The present composition contains a calcium compound, derivatives
thereof or any combination of calcium compound and derivatives thereof.
Preferably, the calcium is present in the composition in an amount
ranging from about 400 mg to about 2,500 mg. More preferably, the calcium
is present in the composition in an amount ranging from about 600 mg to
about 1,800 mg. Even more preferably, the calcium is present in the
composition in an amount ranging from about 800 mg to about 1,600 mg.
Most preferably, the calcium is present in the composition in an amount
ranging, from about 1,000 mg to about 1,400 mg.

[0121]The proportion of total fatty acids to total calcium content in the
present inventions is a critical feature.

[0122]Where three fatty acid compounds are present, preferably, the weight
ratio of the sum of the amounts of the first, second and third fatty acid
compounds to the amount of said calcium compound or derivative thereof is
about 1:0.4 to 50. More preferably, the weight ratio of the sum of the
amounts of the first, second and third fatty acid compounds to the amount
of said calcium compound or derivative thereof is about 1:4 to 20. Even
more preferably, the weight ratio of the sum of the amounts of the first,
second and third fatty acid compounds to the amount of said calcium
compound or derivative thereof is about 1:7 to 15. Most preferably, the
weight ratio of the sum of the amounts of the first, second and third
fatty acid compounds to the amount of said calcium compound or derivative
thereof is about 1:10 to 14.

[0123]The fatty acids of the present inventive subject matter may be used
as such or as biologically acceptable and physiologically equivalent
derivatives as, for example, detailed later herein. Reference to any of
the fatty acids including reference in the claims is to be taken as
including reference to the acids when in the form of such derivatives.
Equivalence is demonstrated by entry into the biosynthetic pathways of
the body as evidence by effects corresponding to those of the acids
themselves or their natural glyceride esters. Thus, indirect
identification of useful derivatives is by their having the valuable
effect in the body of the fatty acid itself, but conversion, for example,
of gamma-linolenic acid to dihomo-gamma-linolenic acid and on to
arachidonic acid can be shown directly by gas chromatographic analysis of
concentrations in blood, body fat, or other tissue by standard
techniques, well known to persons of ordinary skill in the art to which
the present inventive subject matter pertains.

[0124]Derivatives of linoleic acid, as used in the present inventive
subject matter, include, without limitation, salts of linoleic acid,
alkaline salts of linoleic acid, esters of linoleic acid and combinations
thereof. Derivatives of linolenic acid, as used in the present inventive
subject matter, include, without limitation, salts of linolenic acid,
alkaline salts of linolenic acid, esters of linolenic acid and
combinations thereof. The salts and alkaline salts herein refer to those
regularly used organic or inorganic salts which are acceptable for
pharmaceutical use. Non-limiting exemplary linolenic acids include
gamma-linoleic acid and dihomo-gamma-linolenic acid.

[0126]Calcium compounds include, but are not limited to, any of the well
known calcium supplements, such as calcium carbonate, calcium sulfate,
calcium oxide, calcium hydroxide, calcium apatite, calcium
citrate-malate, bone meal, oyster shell, calcium gluconate, calcium
lactate, calcium phosphate, calcium levulinate, and the like. Derivatives
of calcium compounds, as used herein, include, without limitation, salts
of calcium, alkaline salts of calcium, esters of calcium, and
combinations thereof. The salts and alkaline salts herein refer to those
regularly used organic or inorganic salts which are acceptable for
pharmaceutical use. The calcium of the present composition may be from
any source, without limitation.

[0127]Folic acid is also incorporated into the composition of the present
inventive subject matter. Preferably, folic acid is present in an amount
ranging from about 0.4 mg to about 5.0 mg. More preferably, folic acid is
present in an amount ranging from about 0.6 mg to about 1.3 mg. Even more
preferably, folic acid is present in an amount ranging from about 0.8 mg
to about 1.2 mg. Most preferably, folic acid is present in an amount
ranging from about 0.9 mg to about 1.1 mg.

[0129]When vitamin C is present in the composition of the present
inventive subject matter, it is preferably present in an amount ranging
from about 10 mg to about 600 mg. More preferably, the vitamin C is
present in an amount ranging from about 25 mg to about 500 mg. Even more
preferably, the vitamin C is present in an immediate release form in an
amount ranging from about 25 mg to about 50 mg. Most preferably, the
vitamin C is present in a controlled release form in an amount ranging
from about 250 mg to about 500 mg.

[0130]When vitamin E is present in the composition of the present
inventive subject matter, it is preferably present in an amount ranging
from about 5 mg to about 500 mg. More preferably, the vitamin E is
present in an amount ranging from about 10 mg to about 400 mg. Even more
preferably, the vitamin E is present in a controlled release form in an
amount ranging from about 250 mg to about 400 mg. Most preferably, the
vitamin E is present in an immediate release form in an amount ranging
from about 10 mg to about 50 mg.

[0131]Vitamin B6 may also be present in the composition of the present
inventive subject matter. Vitamin B6 is preferably present in an amount
ranging from about 5 mg to about 200 mg. More preferably, vitamin B6 is
present in an amount ranging from about 10 mg to about 50 mg. Even more
preferably, vitamin B6 is present in an amount ranging from 15 mg to
about 40 mg. Most preferably, vitamin B6 is present in a controlled
release form in an amount ranging from 20 mg to about 30 mg.

[0132]Vitamin B12 may also be incorporated into the present composition.
Preferably, the vitamin B12 is present in an amount ranging from about 25
mcg to about 75 mcg. More preferably, the vitamin B12 is present in an
amount ranging from about 35 mcg to about 65 mcg. Even more preferably,
the vitamin B12 is present in an amount ranging from about 40 mcg to
about 60 mcg. Most preferably, the vitamin B12 is present in an amount
ranging from about 45 mcg to about 55 mcg.

[0133]Vitamin D may also be incorporated into the present composition.
Preferably, vitamin D is present in an amount ranging from about 200 IU
to about 625 IU. More preferably, vitamin D is present in an amount
ranging from about 300 IU to about 500 IU. Even more preferably, vitamin
D is present in an amount ranging from about 350 IU to about 450 IU. Most
preferably, vitamin D is present in an amount, ranging from about 375 IU
to about 425 IU.

[0134]Vitamin A may also be incorporated into the present composition.
Preferably, vitamin A is present in the composition in an amount ranging
from about 2,500 IU to about 6,500 IU. More preferably, vitamin A is
present in the composition in an amount ranging from about 4,000 IU to
about 6,000 IU. Even more preferably, vitamin A is present in the
composition in an amount ranging from about 4,500 IU to about 5,500 IU.
Most preferably, vitamin A is present in the composition in an amount
ranging from about 4,750 IU to about 5,250 IU.

[0135]Magnesium, when present, is preferably in the composition of the
present inventive subject matter in an amount ranging from about 25 mg to
about 400 mg. More preferably, magnesium is present in the composition of
the present inventive subject matter in an immediate release form in an
amount ranging from about 25 mg to about 100 mg. Even more preferably,
magnesium is present in the composition of the present inventive subject
matter in a controlled release form in an amount ranging from about 100
mg to about 400 mg. Acceptable magnesium compounds which may be
incorporated into the present inventive subject matter include, but are
not limited to, magnesium stearate, magnesium carbonate, magnesium oxids,
magnesium hydroxide and magnesium sulfate.

[0138]If the non-nutritional active is a hormone, the hormone is
administered in a dosage amount ranging from about 0.15 mg to about 11.25
mg. If the non-nutritional active is an osteoporotic, the osteoporotic is
administered in a dosage amount ranging from about 2.5 mg to about 60 mg.

[0143]The compositions, methods and drug delivery regimens of the present
inventive subject matter may facilitate the simultaneous administration
of storage-incompatible substances, particularly storage incompatible
substances tailored to the needs of premenopausal and menopausal women.
Storage-incompatible substances may be any substances that may not be
formulated together in a single dosage unit or stored together in direct
contact because the substances will interact in a negative manner and
also substances that cannot be formulated together in a single dosage
unit because the sum total of the dosage amounts of the substances would
result in a single dosage unit which is too large to be swallowed.
Storage-incompatible substances also include those substances which may
be stored in direct contact, however, one of the substances is preferably
formulated in a dosage form which is either not preferred or incompatible
with he other substance. The storage-incompatible substances may include
any storage-incompatible substances, without limitation.

[0144]For example, the storage incompatible substances may be hydrophobic
compounds and hydrophilic compounds, olefinic compounds and non-olefinic
compounds, pH sensitive and non-pH sensitive compounds, substances
requiring an anhydrous environment and substances requiring a
non-anhydrous environment, acidic drugs and basic drugs, effervescent
tablets and high water content drugs or dosage forms, gelatin capsules
and aldehydes, quaternary ammonium compounds and anionic substances or
any combination of the above.

[0145]Storage incompatible substances also include substances that cannot
be formulated together in a single dosage unit because the sum total of
the dosage amounts of the substances results in a single dosage unit too
large to swallow. The compositions, methods and drug delivery regimens of
the present inventive subject matter address this problem by separating
the large dosage into multiple doses small enough to swallow comfortably,
while keeping all of the substances and doses together in one package.

[0147]It is also possible in the nutritional composition of the present
inventive subject matter for the dosage form to combine any forms of
release well known to persons of ordinary skill in the art. These
include, without limitation, immediate release, extended release, pulse
release, variable release, controlled release, timed release, sustained
release, delayed release, long acting, and combinations thereof. The
ability to obtain immediate release, extended release, pulse release,
variable release, controlled release, timed release, sustained release,
delayed release, long acting characteristics and combinations thereof is
performed using well known procedures and techniques available to the
ordinary artisan. Each of these specific techniques or procedures for
obtaining the release characteristics does not constitute an inventive
aspect of this inventive subject matter all of which procedures are well
known to those of ordinary skill in the art. As used herein, a
"controlled release form" means any form having at least one component
formulated for controlled release. As used herein, "immediate release
form" means any form having all its components formulated for immediate
release.

[0149]The following procedures represent, without limitation, acceptable
methods of preparing formulations falling within the scope of the
inventive subject matter. For example, animal feed may be made by methods
well known to persons of ordinary skill in the art. Animal feeds may be
prepared by mixing the formulation with binding ingredients to form a
plastic mass. The mass is then extruded under high pressure to form
tubular (or "spaghetti-like") structures that are cut to pellet size and
dried.

[0150]Quick dissolve tablets may be prepared, for example, without
limitation, by mixing the formulation with agents such as sugars and
cellulose derivatives, which promote dissolution or disintegration of the
resultant tablet after oral administration, usually within 30 seconds.

[0151]Cereal coatings may be prepared, for example, without limitation, by
passing the cereal formulation, after it has been formed into pellets,
flakes, or other geometric shapes, under a precision spray coating device
to deposit a film of active ingredients, plus excipients onto the surface
of the formed elements. The units thus treated are then dried to form a
cereal coating.

[0152]For example, health bars may be prepared, without limitation, by
mixing the formulation plus excipients (e.g., binders, fillers, flavors,
colors, etc.) to a plastic mass consistency. The mass is then either
extended or molded to form "candy bar" shapes that are then dried or
allowed to solidify to form the final product.

[0153]Soft gel or soft gelatin capsules may be prepared, for example,
without limitation, by dispersing the formulation in an appropriate
vehicle (vegetable oils are commonly used) to form a high viscosity
mixture. This mixture is then encapsulated with a gelatin based film
using technology and machinery known to those in the soft gel industry.
The industrial units so formed are then dried to constant weight.

[0154]Chewable tablets, for example, without limitation, may be prepared
by mixing the formulations with excipients designed to form a relatively
soft, flavored, tablet dosage form that is intended to be chewed rather
than swallowed. Conventional tablet machinery and procedures, that is
both direct compression and granulation, i.e., or slugging, before
compression, can be utilized. Those individuals involved in
pharmaceutical solid dosage form production are well versed in the
processes and the machinery used as the chewable dosage form is a very
common dosage form in the pharmaceutical industry.

[0155]Film coated tablets, for example, without limitation, may be
prepared by coating tablets using techniques such as rotating pan coating
methods or air suspension methods to deposit a contiguous film layer on a
tablet. This procedure is often done to improve the aesthetic appearance
of tablets, but may also be done to improve the swallowing of tablets, or
to mask an obnoxious odor or taste, or to improve the usual properties of
an unsightly uncoated tablet.

[0156]Compressed tablets, for example, without limitation, may be prepared
by mixing the formulation with excipients intended to add binding
qualities to disintegration qualities. The mixture is either directly
compressed or granulated then compressed using methods and machinery
quite well known to those in the industry. The resultant compressed
tablet dosage units are then packaged according to market need, i.e.,
unit dose, rolls, bulk bottles, blister packs, etc.

[0157]The present inventive subject matter contemplates nutritional
compositions formulated for administration by any route, including
without limitation, oral, buccal, sublinqual, rectal, parenteral,
topical, inhalational, injectable and transdermal. The physicochemical
properties of nutritional compositions, their formulations, and the
routes of administration are important in absorption. Absorption refers
to the process of nutritional composition movement from the site of
administration toward the systemic circulation. Most orally administered
nutritional compositions are in the form of tablets or capsules primarily
for convenience, economy, stability, and patient acceptance. They must
disintegrate and dissolve before absorption can occur. Using the present
inventive subject matter with any of the above routes of administration
or dosage forms is performed using well known procedures and techniques
available to the ordinary skilled artisan.

[0158]The present inventive subject matter contemplates the use of
biologically-acceptable carriers which may be prepared from a wide range
of materials. Without being limited thereto, such materials include
diluents, binders and adhesives, lubricants, plasticizers, disintegrants,
colorants, bulking substances, flavorings, sweeteners and miscellaneous
materials such as buffers and adsorbents in order to prepare a particular
medicated composition.

[0159]Binders may be selected from a wide range of materials such as
hydroxypropylmethylcellulose, ethylcellulose, or other suitable cellulose
derivatives, povidone, acrylic and methacrylic acid co-polymers,
pharmaceutical glaze, gums, milk derivatives, such as whey, starches, and
derivatives, as well as other conventional binders well known to persons
skilled in the art. Exemplary non-limiting solvents are water, ethanol,
isopropyl alcohol, methylene chloride or mixtures and combinations
thereof. Exemplary non-limiting bulking substances include sugar,
lactose, gelatin, starch, and silicon dioxide.

[0160]The plasticizers used in the dissolution modifying system are
preferably previously dissolved in an organic solvent and added in
solution form. Preferred plasticizers may be selected from the group
consisting of diethyl phthalate, diethyl sebacate, triethyl, citrate,
cronotic acid, propylene glycol, butyl phthalate, dibutyl sebacate,
caster oil and mixtures thereof, without limitation. As is evident, the
plasticizers may be hydrophobic as well as hydrophilic in nature.
Water-insoluble hydrophobic substances, such as diethyl phthalate,
diethyl sebacate and caster oil are used to delay the release of
water-soluble vitamins, such as vitamin B6 and vitamin C. In contrast,
hydrophilic plasticizers are used when water-insoluble vitamins are
employed which aid in dissolving the encapsulated film, making channels
in the surface, which aid in nutritional composition release.

[0161]The composition of the present inventive subject matter may be
administered in a partial, i.e., fractional dose, one or more times
during a 24 hour period, a single dose during a 24 hour period of time, a
double dose during a 24 hour period of time, or more than a double dose
during a 24 hour period of time. Fractional, double or other multiple
doses may be taken simultaneously or at different times during the 24
hour period. The doses may be uneven doses with regard to one another or
with regard to the individual components at different administration
times. For example, without limitation, the amount of calcium in a
morning dose is different from the amount of calcium in an evening dose.

[0162]The compositions of the present invention are intended for use by
humans and other mammals. The dosages are adjusted according to body
weight and thus may be set forth herein on a per body weight basis. For
example, if the formula specifies a range of about 10-1000 mg for a 55 kg
individual, that range would be adjusted for a 35 kg individual to about
6.3-63 mg (e.g., the lower range limit=(35 kg/55 kg)*10 mg=6.3 mg).
Decimal amounts may be rounded to the nearest whole number. In the above
manner the present compositions may thus be adapted to be suitable for
any individual, including any mammal, regardless of its size.

[0163]The present composition is adapted to meet the specific
physiological needs of a menopausal woman. For example, the formulations
may focus on special nutritional needs of a menopausal woman that are not
generally or adequately addressed in nutritional dietary supplements,
such as essential fatty acids, without limitation. The iron and calcium,
when present, are provided in amounts to optimize nutritional benefit to
the menopausal woman, while minimizing unpleasant side effects which may
accompany overly large doses. The formulation can be further tailored
based upon the specific needs, genetic predispositions or identified
deficiencies of individual women, on either a generalized or case by case
basis for greater specificity. Further, the composition may be
specifically adapted for treating conditions associated with menopause or
to maximize neurological maintenance of a menopausal woman. The
composition may also be adapted for inhibiting loss in bone mass and
preventing deficiency of essential acids in menopausal women. Moreover,
the present composition can be used as one component of a prescribed
therapy.

[0164]The composition of the inventive subject matter may be provided in a
blister pack or other such pharmaceutical package, without limitation.
Further, the compositions of the present inventive subject matter may
further include or be accompanied by indicia allowing women to identify
the compositions as products for menopausal women. The indicia may
further additionally include an indication of the above specified time
periods for using said compositions.

[0165]For example, without limitation, the indicia may be time indicia
indicating a specific or general time of day for administration of the
composition, or the indicia may be a day indicia indicating a day of the
week for administration of the composition.

[0166]The composition of the present invention may be used prior to and
during menopause. Use of the compositions may commence at the onset of
menopause. The composition of the present inventive subject matter is
preferably administered during a period commencing no later than the
appearance of the first symptoms associated with menopause and continuing
throughout a woman's life. More preferably, the composition is
administered during a period of time commencing just prior to menopause
or just prior to any symptoms of menopause. The phrases "just prior to
menopause" and "prior to any symptoms of menopause" are intended herein
to include commencement of administration of compositions approximately
one month to five years prior to an age generally identified with
initiation of menopause.

[0167]Preferably, the commencement of administration of the composition is
when the woman is thirty five to fifty years of age. More preferably, the
commencement of administration is one month prior to the woman turning
forty years of age. Even more preferably, the commencement of
administration is one year prior to the woman turning forty years of age.
Most preferably, the commencement of administration five years prior to
the woman turning forty years of age.

[0168]The present inventive subject matter includes a method for providing
nutritional supplementation to a menopausal woman. The methods include
administration of the present composition to women during a critical
period. The critical period of administration is the period commencing
just prior to menopause and continuing through the postmenopausal period
of a woman's life.

[0169]The method of the present inventive subject matter may prevent or at
least minimize fatty acid deficiency in menopausal women. The present
method may also be used to prevent or treat symptoms associated with
menopause. Further, the present method may inhibit the loss in bone mass
commonly experienced by menopausal women. The present method may delay
onset or menopause and/or reduce possibility of premature menopause.

[0170]The present methods may be carried out alone or in conjunction with
a therapeutic therapy or regimen, without limitation. The therapeutic
therapy or regimen may be for treating symptoms associated with menopause
or may be entirely unrelated to menopause. For example, without
limitation, the present method may be incorporated as part of hormonal or
estrogen therapy, or in combination with dietary manipulation.

[0171]The foregoing is considered as illustrative only of the principles
of .the inventive subject matter. Further, since numerous modifications
and changes will readily occur to those skilled in the art, it is not
desired to limit the inventive subject matter to the exact construction
and operation shown and described, and accordingly all suitable
modifications and equivalents may be resorted to, falling within the
scope of the inventive subject matter.

[0172]The following examples are illustrative of preferred embodiments of
the inventive subject matter and are not to be construed as limiting the
inventive subject matter thereto. All percentages are based on the
percent by weight of the final delivery system or formulation prepared
unless otherwise indicated and all totals equal 100% by weight.

EXAMPLES

Example 1

[0173]The following formulations are used to prepare compositions for
administration to premenopausal and menopausal women:

[0174]It would be anticipated that upon administration of the above
composition, an average normal menopausal woman would be expected to have
reduced incidence of nutritional deficiency and reduced
menopausal-related symptoms or disorders when compared to an average
normal menopausal woman following a conventional nutritional regimen.

Example 2

[0175]The following compositions are for administration to premenopausal
women and menopausal women in accordance with the regimen indicated
below:

[0176]It would be anticipated than upon following the above regimen, an
average normal menopausal woman would be expected to have reduced
incidence of nutritional deficiency and reduced menopausal-related
symptoms or disorders when compared to an average normal menopausal woman
following a conventional nutritional regimen.

Example 3

[0177]A soft gelatin supplement in accordance with the compositions of
Examples 1 and 2 above, may be prepared, by first combining mineral oil
and soybean oil in a first vessel and blending it to form a uniform oil
mixture, heating the oil mixture to 45 degrees Celsius, and then adding
propylene glycol. In a second vessel preheated to 70 degrees Celsius,
yellow beeswax and soybean oil are added and blended until a uniform wax
mixture is formed. The wax mixture is cooled to 35 degrees Celsius and
then added to the oil mixture. To this combined oil and wax mixture,
folic acid, vitamin B6, iron, magnesium, and calcium are then added
and blended together to form a uniform biologically active mixture. The
mixture is then cooled to 30 degrees Celsius to form a viscous
biologically active core composition, after which time the composition is
ready for encapsulation in a soft gelatin shell.

[0178]A soft gelatin shell is prepared by heating purified water in a
suitable vessel and then adding gelatin. This water gelatin mixture is
mixed until the gelatin is fully dissolved, and then glycerin,
preservatives, one or more flavors, and one or more colorants are added.
This gelatin mixture is blended well and cooled. The shells are then
filled with the core composition and formed in accordance with soft
gelatin techniques commonly used and well known to persons of skill in
the art.

Example 4

[0179]The following compositions are for administration to premenopausal
women and menopausal women in accordance with the regimen indicated
below:

[0180]It would be anticipated that upon following the above regimen, an
average normal menopausal woman would be expected to have reduced
incidence of nutritional deficiency and reduced menopausal-related
symptoms or disorders when compared to an average normal menopausal woman
following a conventional nutritional regimen.

Example 5

[0181]The following compositions are for administration to premenopausal
women and menopausal women in accordance with the regimen indicated
below:

[0182]It would be anticipated that upon following the above regimen, an
average normal menopausal woman would be expected to have reduced
incidence of nutritional deficiency and reduced menopausal-related
symptoms or disorders when compared to an average normal menopausal woman
following a conventional nutritional regimen.

[0183]The inventive subject matter being thus described, it will be
apparent that the same may be varied in many ways. Such variations are
not to be regarded as a departure from the spirit and scope of the
inventive subject matter, and all such modifications are intended to be
within the scope of the appended claims.